Project Summary: The overall goal of this proposed research is to estimate the effects of genetic factors on risk of prostate and bladder cancers in two established studies chosen for their distinct design and methodology as well as the candidate's experience and familiarity with the two study populations. The first aim will focus on African American men with inherited forms of prostate cancer participating in the Prostate Cancer Genetics Project. We will perform follow-up investigations of a recent finding suggesting linkage on chromosome 22 among African American families participating in this large family-based study designed to localize one or more prostate-cancer susceptibility genes. We also plan to develop new recruitment strategies to increase participation of African American families to more fully characterize the clinical and genetic characteristics of African Americans with hereditary prostate cancer. The second aim of the project focuses on genetic modifiers of arsenic-mediated bladder cancer risk. We have proposed to investigate the association of several candidate genes that are suspected of influencing the methylation of inorganic arsenic and bladder-cancer risk. We will pool our data with collaborators from the New England Study of Environment and Health to estimate the separate and joint effects of genotype and arsenic exposure. This research plan, which involves the use of largely traditional approaches of genetic analysis to explore novel areas of genetic research, coupled with the proposed formal genetic coursework and experience in a genetics laboratory will serve to broadly develop the genetic training of a cancer epidemiologist who plans to devote her research career to the study of urologic cancers. Relevance: Cancers of the prostate and urinary bladder are two of the most common cancers diagnosed in the United States with strong evidence that genetic susceptibility is an important factor in the development of both cancers. Identifying individuals with an inherited predisposition would be important in developing strategies for the primary prevention and or early detection of disease.